Role of TNFRSF1A and TNFRSF1B polymorphisms in susceptibility, severity, and therapeutic efficacy of etanercept in human leukocyte antigen-B27-positive Chinese Han patients with ankylosing spondylitis.

Abstract

The successful therapeutic use of anti-TNF biological agents in patients with ankylosing spondylitis (AS) indicates that tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor (TNFR) genes are involved in the pathogenesis of AS. TNF-α exerts its biological activity by binding to its cell surface receptors (p55 TNF-α receptor [TNFRI, encoded by the Tumor Necrosis Factor Receptor Superfamily Member 1A (TNFRSF1A)] and p75 receptor [TNFRII, encoded by the Tumor Necrosis Factor Receptor Superfamily Member 1B (TNFRSF1B)]. TNFRSF1A and TNFRSF1B may be related to AS, but the relevant studies are still limited. Therefore, we aim to explore the association between TNFRSF1A and TNFRSF1B polymorphisms and susceptibility and short- and long-term response to anti-TNF treatment in human leukocyte antigen-B27 (HLA-B27)-positive Chinese Han patients with AS.A total of 215 HLA-B27-positive patients with AS and 216 HLA-B27-positive matched controls were enrolled and genotyped for rs767455, rs2234649, and rs1061622. A subset of 50 AS patients was also studied for the association of these polymorphisms with the short- and long-term response to etanercept assessed by Assessment in Ankylosing Spondylitis 20 (ASAS20) and Assessment in Ankylosing Spondylitis 40 (ASAS40).Our data showed that rs767455 was associated with the susceptibility of AS, G allele of rs767455 exhibited an association with the risk of developing AS (OR = 1.63 (1.04–2.55), P = .032). Rs1061622 polymorphism was associated with total back pain and chest expansion. Only rs1061622 was significantly associated with long-term efficacy of etanercept: the TG genotype of rs1061622 worsened ASAS20 and ASAS40 responses at 12 months (P = .021 and .041, respectively).The results suggest that TNFRSF1A and TNFRSF1B polymorphisms were associated with susceptibility, severity, and the long-term therapeutic efficacy of etanercept of patients with AS.